The present invention relates to compositions comprising finafloxacin and Tris. Such compositions may represent pharmaceutically acceptable parenteral compositions and can be used for the treatment of bacterial infections such as urinary tract infections, intra-abdominal infections, skin and soft tissue infections, diabetic foot infections, bacteremia, and respiratory tract infections.
Finafloxacin (INN International Nonproprietary name) is an antibiotic of the class of the quinolone carboxylic acids of the following formula: (−)-8-cyano-1-cyclopropyl-6-fluoro-7-[(4aS,7aS)-hexahydropyrrolo[3,4-b]-1,4-oxazin-6(2H)-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. Finafloxacin and derivatives thereof can be synthesized according to the methods described in WO 98/26779 by Matzke et al., the contents of which are herein incorporated by reference in their entirety. Finafloxacin has been described as useful in the treatment of H. pylori infections (EP0946176) or of ophthalmic, otic, or nasal infections (U.S. Pat. No. 8,536,167).
WO 98/26779, EP0946176 or U.S. Pat. No. 8,536,167 do not describe any pharmaceutical preparations which are suitable for the parenteral administration. Parenteral administration of drugs is especially crucial for the treatment of intensive care patients which are often not able to take oral medication but it can also help to quickly reduce the number of pathogens in an infection site due to the rapid delivery of the drug into the blood stream.
For a parenteral use, finafloxacin must be formulated as a stable, efficacious composition comprising a pharmaceutically sufficient amount of the active ingredient in an acceptable small volume in order to be usable as a parenteral application, i.e. relatively high concentrations of finafloxacin dissolved reliably and stable. The degradation of the active pharmaceutical ingredient or an excipient must be avoided when stored for a period of time.
It is known that the solubility characteristics are a general problem by using and handling finafloxacin. The solubility of finafloxacin is regarded to be not sufficient to generate physically stable solutions of high enough concentration at acceptable pH values to effectively treat infections in physiological solvents. The instability manifests itself by the formation of sub-visible and visible particles during storage. In addition, due to the poor solubility of finafloxacin there is the problem of administering a composition containing, e.g., 200 mg to 1000 mg or more of the active compound in an acceptable volume of parenteral applicable solution.
Thus, there is the need for compositions containing sufficient amounts of finafloxacin in acceptable volumes, and having also long term stability characteristics so such compositions can be used as pharmaceutically parenteral compositions.